A major aim of this Center is to perform translational clinical research closely linked to advances in fundamental knowledge on pain pharmacology, generated in each of the laboratory Projects. As such, a major focus and goal of Project V is to provide continuous interaction between laboratory and clinical investigators and projects. This process is aimed at refining both the laboratory and clinical hypotheses and to generate novel, testable concepts. All clinical protocols within this Center are designed, implemented, analyzed, and communicated internally by Project V. This includes proper power analysis, use of innovative study designs, collection of additional experimental data to support new methodologies, support for regulatory agency application, both at the institutional and federal level, consistent application of psychophysical testing, and standardization of methods to allow efficient comparison of results across studies. Dr. Rauck will be primarily responsible for the studies in volunteers and postoperative patient, Dr. Tobin will be responsible for the PET studies, and Dr. Coghill for psychophysical testing across all studies. Project V will examine, in four clinical trials, hypotheses generated by Projects I-IV, as well as its own hypotheses in psychophysics from Dr. Coghill. Included in these trials will be critical testing of the applicability of new methodology (i.e., a novel, more efficient, and clinically relevant approach to the study of analgesic drug interactions); examination of the predictive value of results in experimental models of pain in normal volunteers to subacute and chronic clinical pain settings; and determination of the contribution of hypersensitivity to the overall pain experience in patients following surgery and those with neuropathic pain. Unique pharmacologic tools available only at this institution will be utilized in these trials, and these trials will significantly advance the aims of the Center and our understanding of the pharmacology of pain in humans.